Elevated matrix metalloproteinase-9 levels in neuronal extracellular vesicles in Alzheimer's disease

This study aimed to investigate plasma neuronally derived extracellular vesicle (NDEV) levels of core pathological markers [amyloid-β (Aβ) and phosphorylated tau] and inflammatory biomarkers, including interleukin 6 (IL-6) and matrix metalloproteinase-9 (MMP-9) in patients with Alzheimer's disease (AD).

Thirty-one patients with AD and 15 cognitively normal controls (NCs) were recruited. The diagnosis of AD was supported by fluorodeoxyglucose and Pittsburgh Compound-B PET scans. Plasma extracellular vesicles were extracted, precipitated, and enriched for neuronal source by anti-L1CAM antibody absorption. Levels of Aβ42, P-T181-tau, P-S396-tau, IL-6, and MMP-9 in plasma NDEVs were quantified by enzyme-linked immunosorbent assay (ELISA).

Aβ42, P-T181-tau, and MMP-9 levels in plasma NDEVs were significantly higher in patients with AD than NCs. However, P-S396-tau and IL-6 levels in plasma NDEVs did not differ between AD patients and NCs. Moreover, there was no correlation between any of these biomarker levels and cognitive function as measured with Mini-Mental State Examination in patients with AD.

These findings provide further support that levels of core pathological markers, including Aβ42 and P-T181-tau, are elevated in plasma NDEVs of patients with AD. Furthermore, MMP-9 might play an important role in the pathogenesis of AD, and is a promising inflammatory biomarker for AD.